Severe Necrotizing Adenovirus Tubulointerstitial Nephritis in a Kidney Transplant Recipient

Abstract

Adenoviruses (AdV) are emerging pathogens with a prevalence of 11% viruria and 6.5% viremia in kidney transplant recipients. Although AdV infection is common, interstitial nephritis (ADVIN) is rare with only 13 biopsy proven cases reported in the literature. We report a case of severe ADVIN with characteristic histological features that includes severe necrotizing granulomatous lesion with widespread tubular basement membrane rupture and hyperchromatic smudgy intranuclear inclusions in the tubular epithelial cells. The patient was asymptomatic at presentation, and the high AdV viral load (quantitative PCR>2,000,000 copies/mL in the urine and 646,642 copies/mL in the serum) confirmed the diagnosis. The patient showed excellent response to a combination of immunosuppression reduction, intravenous cidofovir, and immunoglobulin therapy resulting in complete resolution of infection and recovery of allograft function. Awareness of characteristic biopsy findings may help to clinch the diagnosis early which is essential since the disseminated infection is associated with high mortality of 18% in kidney transplant recipients. Cidofovir is considered the agent of choice for AdV infection in immunocompromised despite lack of randomized trials, and the addition of intravenous immunoglobulin may aid in resolution of infection while help prevention of rejection.

Granulomatous inflammation in BK polyomavirus–associated nephropathy

“…As expected in immunosuppressive states, the vast majority of cases are secondary to infections, among which mycobacterial and fungal etiologies predominate . In addition, viral infections, in particular adenovirus nephritis and less commonly cytomegalovirus infections may cause granulomatous inflammation . Similarly to the native kidney, hypersensitivity (allergic) granulomatous interstitial nephritis and sarcoidosis can also affect renal allografts …”

“…9,[17][18][19][20][21] In addition, viral infections, in particular adenovirus nephritis and less commonly cytomegalovirus infections may cause granulomatous inflammation. 2,9,18,[22][23][24][25] Similarly to the native kidney, hypersensitivity (allergic) granulomatous interstitial nephritis and sarcoidosis can also affect renal allografts. 15,16,21,24 Tubulointerstitial inflammation of any etiology requires differentiation from acute and chronic active T-cell-mediated allograft rejection in renal allograft biopsies.…”

Cystite hémorragique à adénovirus chez le transplanté rénal : à propos d’un premier cas en Afrique noire survenu dans un tout débutant programme de greffe rénale et revue de la littérature

“…Quatre-vingts (80) cas d'infections par l'adé novirus ont é té rapporté s chez le transplanté ré nal [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] (Tableau 1). Il s'agit d'une affection qui touche aussi bien les hommes que les femmes, avec une lé gè re pré dominance fé minine (35 hommes pour 44 femmes), et survient à tout âge (âge moyen 39 ans ; extrêmes allant de 5 à 80 ans).…”

Infectious Diseases and the Kidney in Children

“…Adenovirus types 11 and 21 are the usual strains isolated. It has been implicated in causing necrotizing granulomatous tubulointerstitial nephritis in transplant recipients, primarily affecting the distal nephron [174,175]. The prevalence of viremia in adult transplant recipients is estimated at 6.5 %.…”

“…The prevalence of viremia in adult transplant recipients is estimated at 6.5 %. Case reports in adults have reported treatment with immunosuppressant reduction, intravenous cidofovir, and immunoglobulin to try and prevent rejection [175].…”